Nucleosides, Nucleotides & Nucleic Acids最新文献

A novel acid-cleavable triazene linker was synthesized and then reacted with modified 2'-deoxyuridine triphosphate (dUTP), followed by Cy3 NHS ester, the final product serves as an excellent reversible terminator for DNA sequencing by synthesis (DNA SBS). The synthesized dye-labeled terminator incorporated into DNA strand faithfully in a DNA-elongation, and the fluorophore incorporated into DNA strands was cleaved completely under weak acidic conditions within short time. Further the first cleaved product can be incorporated with 100% efficiency for the second time. These preliminary evaluations show that the triazene reversible terminator has a great potential value in DNA sequencing.

Vascular calcification is a common complication of chronic kidney disease (CKD). The molecular mechanisms underlying this condition and the efficacy of potential treatments remain unclear. Bioinformatic methods were employed to analyze gene ontology (GO) annotations and pathway enrichments. Subsequently, an analysis of potential therapeutic agents for vascular calcification in CKD was performed. A total of 76 common genes, 181 enriched GO annotations-comprising 153 biological processes, 10 cellular components, and 18 molecular functions-41 KEGG pathways, 13 REACTOME pathways, and 3 BIOCARTA pathways were identified. Five key genes (PSMC5, TNFSF11, TNFRSF11A, TNFRSF12A, and ICAM1) were isolated. Most notably, the top five potential therapeutic drugs-ENAVATUZUMAB, DENOSUMAB, ALICAFORSEN, BI-505, and ENLIMOMAB PEGOL-were identified for vascular calcification in CKD. However, further molecular biological experiments are required to confirm these findings.

The substances that cause abnormal DNA structures are known as DNA damage-inducing factors, and their resulting DNA damage has been extensively studied and proven to be closely related to cancer, neurodegenerative diseases, and aging. Prolonged exposure to DNA damage-inducing factors can lead to a variety of difficult-to-treat diseases, yet these factors have not been well summarized. It is crucial to use a combination of environmental science and life science to gain a deep understanding of the environmental sources and biological consequences of DNA damage-inducing factors for mechanistic research and prevention of diseases such as cancer. This article selected 14 representative carcinogenic exogenous DNA damage-inducing factors and summarized them through a literature search, including both exogenous and endogenous DNA damage factors, and explored the types of DNA damage caused by the relevant damage factors.

Introduction: Dental pulp stem cells (DPSCs) have the potential to differentiate into various types of tissues including tooth, adipose, cartilage, muscle, nerve, and also possess regenerative properties. Harmine, a beta-carboline alkaloid, has been shown to have antitumor activities and promote bone formation through the differentiation of osteoblasts. The aim of this study was to investigate the effect of harmine on the differentiation of DPSCs into odontoblast cells.

Materials and methods: DPSCs were obtained from Iran's National Genetic Reserve Center and cultured under standard stem cell culture conditions. The cells were differentiated in culture medium with and without harmine, and cell viability was evaluated using MTT assay at different harmine concentrations. Moreover, differentiation of cells was measured using Alizarin Red staining, and the expression of Runx2, DSPP, and DMP1 genes was evaluated using western blotting and real-time PCR.

Results: Harmine increased the survival rate of DPSCs in a time--dependent manner, but higher doses (above 80 μM) had a toxic effect. On day 14, Alizarin Red staining showed increased differentiation of odontoblasts in the harmine-treated groups compared to the untreated groups. Furthermore, harmine increased the expression of Runx2, DSPP, and DMP1 genes and proteins.

Conclusion: These findings suggest that harmine has a significant impact on the differentiation and proliferation of odontoblasts in DPSCs, likely due to its various properties and role in healing various diseases. Therefore, harmine could serve as a potential therapeutic agent for promoting dental tissue regeneration using DPSCs.

Among the most prominent realizations of Morris J. Robins in the antiviral nucleoside chemistry are (i) the synthesis of 8-substituted (methyl-, amino-, bromo-, iodo) derivatives of acyclovir, (ii) xylotubercidin as an inhibitor of herpes simplex virus (HSV) infections, (iii) the anti-HIV activity of the 2',3'-dideoxyriboside of 2,6-diaminopurine (ddDAPR) and the 3'-azido- and 3'-fluoro derivatives thereof (AzddDAPR and FddDAPR, respectively), (iv) the potentiating effect of ribavirin on the anti-HIV activity of 2',3'-dideoxyinosine (ddI) and ddDAPR, (v) S-adenosylhomocysteine hydrolase (SAH) inhibitors principally active against vaccinia virus (VV) and vesicular stomatitis virus (VSV), and (vi) furo[2,3-d]pyrimidinone derivatives active against varicella-zoster virus (VZV).

Background: Crimean-Congo hemorrhagic fever (CCHF), an acute viral hemorrhagic fever disease, has a high mortality rate among humans. Hemorrhagic propensity is caused by coagulation malfunction and increased capillary permeability brought on by the resultant vascular injury. Vascular endothelial growth factor (VEGF) and VEGF receptor-2, or KDR (kinase insert domain containing receptor), are effective in vasculogenesis and angiogenesis. CCHF was stated to have endothelial dysfunction. This study aimed to evaluate whether the VEGF and KDR gene variants contribute to the development of CCHF in the Turkish population.

Methods: A total of 101 subjects, including 51 CCHF patients and 50 healthy controls, were included in the study. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used to genotype VEGF 936 C > T (rs3025039) and KDR - 604 T > C (rs2071559) variants. The results were statistically analyzed.

Results: The VEGF 936 C > T genotype and allele distributions did differ significantly between the patients and the controls. The subjects carrying the C/C genotype and C allele had a higher risk of developing CCHF than the control group (p˂0.05). There was a statistically significant association between the controls and the patients in terms of VEGF 936 C > T C/C versus C/T + T/T (p˂0.05, OR:3.273, 95%Cl: 1.44-7.63). The KDR - 604 T > C variant's allele and genotype distribution were not significantly different between the patients and controls.

Conclusion: This study suggests the VEGF 936 C > T variant is a genetic marker of sensitivity to CCHF among the Turkish population and may help protect against the disease.

Osteoporosis is a common age-related skeletal disease, characterized by changes in the microarchitectural structure of bone tissue and decreased bone mass, especially affecting postmenopausal women. Genetic and environmental factors affecting bone metabolism play a role in the development of osteoporosis. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in the conversion of homocysteine to methionine. Genetic variations in the MTHFR gene lead to impaired function or inactivation of this enzyme. A decrease in MTHFR enzyme activity and an increase in homocysteine levels affect bone metabolism. In this study, we aimed to investigate the relationship between C677T and A1298C polymorphisms and osteoporosis in Turkish postmenopausal women. DNA samples were extracted from 200 volunteers. The PCR-RFLP technique was used to identify the MTHFR gene polymorphisms C677T and A1298C. The statistical significance of the analysis's results was assessed. C677T genotype and allele frequency distributions were not statistically different between postmenopausal osteoporosis and healthy control groups (p = 0.249, p = 0.754), while A1298C genotype and allele frequency distributions were found to be statistically significant (p = 0.002, p = 0.013). The results of our study showed that the A1298C polymorphism may be a genetic factor associated with osteoporosis in this specific population. However, the C677T polymorphism did not show a significant connection. To gain a more comprehensive understanding of the genetic basis of osteoporosis, future research with larger sample sizes and the consideration of additional genetic and environmental factors is essential. Additionally, it is crucial to account for ethnic disparities, gene-gene interactions, and gene-environment interplays. These insights can inform the development of personalized preventive and therapeutic strategies for individuals at risk of osteoporosis in diverse populations.

Leukemia is a cancer affecting the hematopoietic system with an unclear pathogenesis. Recent studies suggest a correlation between several long non-coding RNAs (lncRNAs) and leukemia development. This study focuses on the potential link between H19 (rs2839698 and rs217727) polymorphisms and Acute Lymphoblastic Leukemia (ALL) susceptibility. The study involved 150 patients with clinically confirmed ALL and 150 controls. This research included 150 Iranian patients, who were confirmed to have clinical ALL, and 150 healthy people as the control group. A kit was utilized to extract the DNA of all the samples. After preparing the samples, DNA genotyping was done by using the tetra-primer ARMS-PCR method. After adjusting for age using multivariate logistic regression analysis, individuals carrying the CT genotype of rs2839698 were found to have a significantly 0.32-fold reduced risk of ALL compared with carriers of the CC genotype. Furthermore, a significant 0.48-fold reduction in ALL risk was observed in patients with CT+TT genotype rs2839698 compared with CC. Moreover, the over-dominant model was applied to compare the CT genotype of rs2839698 with its CC+TT genotype, which showed a significant 0.36-fold reduction of ALL risk. Notably, the cases of ALL and the control group were not significantly different in terms of their genotype and allele frequencies of rs217727 polymorphism. Yet, the TT haplotype was significantly associated with ALL risk (OR: 1.64, p = 0.025). Following the findings of this study, it can be concluded that H19 SNP rs2839698, rather than rs217727, might act as an innovative susceptibility marker for ALL leukemia.

Varkud satellite ribozyme (VS ribozyme) is a class of catalytic RNA with self-cleavage activity. The wild-type VS ribozyme has structural modularity with a relatively large catalytic module (H2-H6 elements) and a small substrate module (H1 element). The two modules can be dissected physically, and the substrate H1 RNA is recognized and then cleaved by the rest of the parent ribozyme serving as catalytic RNA. We characterized the catalytic properties of a bimolecular VS ribozyme developed and employed for an in-droplet evolution experiment of the VS ribozyme. We examined the effects of polyamines and several divalent metal ions. The results obtained in this study would be useful for the optimization of laboratory evolution of the VS ribozyme.